No longer a cog in the wheel
Similar to NFL long snappers, typically contract manufacturers are not the center of media coverage unless something has gone terribly awry. Arch Venture Partners’ co-founder Keith Crandell referred to manufacturing being historically the “weak cousin” in the pharma industry constellation. However, that increasingly is no longer the case.
The critical nature of the work CDMOs perform was thrust into the national spotlight as manufacturing was relied upon to deliver one of the most critical and complex vaccine distribution efforts in history. Gil Roth, president of the Pharma & Biopharma Outsourcing Association (PBOA), an industry advocacy group explained: “Because of the pandemic the CDMO sector has never had a higher profile than it does now. The general public is starting to understand that just because it says [Drug Company X] on the label, that does not mean that is who made the vaccine or therapeutic.”
This heightened awareness of the general public has also meant that Congress and the FDA have been willing to take a deeper look into understanding how the sector works and the essential role manufacturers play in bringing therapies in development to reality.
It helped that companies in the manufacturing space stepped up and delivered despite enormous complications around social distancing, worker safety and supply chain unpredictability. These businesses were deemed essential from the get-go, and many never shut down. Jeff Reingold, COO of Contract Pharmacal Corp, based in Hauppauge NY, offered a story that epitomized the can-do nature of the industry. “When you are a manufacturer you need the machines running, so the safety piece was very stressful. At one point, we had four lunch breaks for one eight hour shift because we were limiting how many people could be in the cafeteria.”
A challenging human resources environment meant that CPC, along with many others in the space, could not manufacture at full capacity, thus had to make decisions around what to produce. “We could not make everything, but we wanted to make sure that what we could make fit within our customers prioritization. Adding to this complexity was the fact that bottles and caps were not available. Lead times on materials were longer and it pushed us to think differently and to focus on what we have, what we are capable to produce, while also considering the timing on future productions based on expectations from our vendors,” said Reingold.
“You might only use the injectable equipment if you are producing one particular drug, one for two days a month, which would not make sense to invest in if you were a pharma company. Whereas if you are a CMO it would make great sense because you can run many different products on that same line. The cost and complexity of equipment has gone up dramatically while the run sizes have gone down. Consequently, it plays into the CMO strategy of investing in biologics capacity.”
Brad Payne, COO, PCI Pharma Services
Speeding to market
For early-stage companies, timelines matter. Funding is tied to timelines and milestones being met. Companies operate within a finite window to achieve proof of concept or progress through a clinical trial, so being marred by delays in the manufacturing process can mean failure. At the later stage, manufacturing holdups also have harsh consequences for the economics of a product, and in cases such as vaccine development, it can mean many additional lives lost. This was evinced by the FDA’s actions asking JNJ to scrap up to 15 million COVID-19 vaccine doses and temporarily halt production over an error made at an Emergent BioSolution's manufacturing site. This means that other vaccine makers such as Moderna and Pfizer will continue to handle the bulk of vaccine production.
CordenPharma represents a leg of the mRNA supply chain, as it was awarded the contract to supply critical lipid excipients for Moderna’s COVID vaccine formulation. When asked about the factors that enabled CordenPharma to move in such a fast manner to bring this product to market, Michael Quirmbach, the company’s CEO and president, responded: “The key is all about having critical size, great teams in place and quickly making the right decisions. When we were approached by Moderna we immediately understood the complexity. We put a global team together, relying on various competencies, and we used our global facility network to scale up rapidly. Initially, work started in Switzerland and soon after, we involved other sites as part of our network.”
Quotient Sciences, which sees itself as a drug development and manufacturing accelerator supporting pharmaceutical and biotech companies, is another company extraordinarily focused on speed to market. Its’ Translational Pharmaceutics platform integrates disciplines around drug product manufacturing and clinical testing that are traditionally found in different silos in the outsourcing industry. By integrating these activities and very closely aligning workflows around manufacturing and clinical testing, Quotient demonstrated that at least 12 months could be saved on the drug development timeline. “The traditional outsourcing paradigm is very siloed, meaning if customers want to do drug product manufacturing, drug substance manufacturing and clinical testing, they would need to go to a separate CDMO or CRO for each of these services,” Quotient Sciences’ CEO Mark Egerton explained. “Quotient’s approach offers a single supply chain managed by a single project team, in which we are able to provide all of these services to our customers all at one organization, which in turn makes a contribution to their time savings or efficiency saving.”
Software assists timelines
When it comes to manufacturing timelines, validation is another area that can be burdensome. The FDA defines validation as “a process that is required to establish documented evidence to assure that a specific system, equipment, computer system, or process will consistently meet the requirements of its intended use.” All organizations need to validate their systems, computers, equipment, and processes that have GMP impact.
This has significant bearing on companies involved in pharmaceutical manufacturing where typically these processes were done manually in addition to being paper based. Usually, with any validation lifecycle process, there are nine different lifecycle stages, and now contract manufacturers are outsourcing their validation work by purchasing software from companies like ValGenesis, who manage each of the nine distinct validation lifecycle stages as a module and connect the dots that flow data from system assessment and author requirements up to the retirement stage. Dr. Siva Samy, CEO and chief product strategist at ValGenesis, explained: “ValGenesis makes the end-to-end validation lifecycle process 100% digital, reducing validation cycle time by over 50% and thus, helping life science companies release their products to market more quickly… Most of our clients are involved in manufacturing lifesaving drugs. Many of their production lines were identified as essential to keep products getting to market on time during the pandemic. With the help of the ValGenesis platform, our clients can now manage the validation process remotely or with limited onsite resources, without any disruption to their supply chain”.
Image courtesy of CordenPharma